title: Direct effects of tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies.
abstract: OBJECTIVE
  Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction.
  
  
  METHODS
  Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms.
  
  
  RESULTS
  A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r(2) = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement.
  
  
  CONCLUSIONS
  Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction.
authors.affiliation: University of Western Ontario, London, Ontario, Canada. Electronic address: gebrock@sympatico.ca.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Brock
authors.affiliation: Department of Urology, Southern Illinois University, Springfield, Illinois.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McVary
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana.
authors.forename: Steven
authors.initials: S
authors.lastname: Watts
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ni
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana.
authors.forename: Lars
authors.initials: L
authors.lastname: Viktrup
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana.
authors.forename: David G
authors.initials: DG
authors.lastname: Wong
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana.
authors.forename: Craig
authors.initials: C
authors.lastname: Donatucci
mesh_terms: D000368:Aged; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D015897:Comorbidity; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000453:epidemiology; D000068581:Tadalafil; D016896:Treatment Outcome
chemical_list: D002243:Carbolines; D000068581:Tadalafil
keywords: BPH; ED; LUTS; PDE5; benign prostatic hyperplasia; erectile dysfunction; lower urinary tract symptoms; phosphodiesterase 5 inhibitors; phosphodiesterase type 5; prostatic hyperplasia; tadalafil